Structure of 192642-85-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 192642-85-6 |
Formula : | C7H6BrNO2 |
M.W : | 216.03 |
SMILES Code : | BrC1=CN=C(C=C1)CC(=O)O |
MDL No. : | MFCD09999983 |
InChI Key : | ATKULCGQSLCGEK-UHFFFAOYSA-N |
Pubchem ID : | 46238459 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.3 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.72 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.27 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.11 |
Solubility | 1.69 mg/ml ; 0.00783 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.68 |
Solubility | 4.47 mg/ml ; 0.0207 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.66 |
Solubility | 0.469 mg/ml ; 0.00217 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.88 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.65 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | [Example 60]tert-Butyl 4-[2-[2-(4-methanesulfonylphenoxyethyl)pyridine-5-yl]piperidine-1-carboxylate (1) 2-(5-Bromopyridin-2-yl)ethanol To a solution of (5-bromopyridin-2-yl)acetic acid (60.0 mg, 0.278 mmol) in dry tetrahydrofuran (1.4 mL) was added dropwise borane- tetrahydrofuran complex (1.06M in tetrahydrofuran, 0.34 mL, 0.361 mmol) under N2. The mixture was stirred at room temperature for 19 hours and water(5 mL)-acetic acid (5 mL) was added slowly. The mixture was concentrated under reduced pressure, the residue was poured into saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/1→ethyl acetate) to give the title compound as a yellow oil (45 mg, yield 80%).1H NMR(CDCl3,400 MHz): δ= 2.98(2H, t, J=5 Hz), 3.68(1H, brs), 4.01(2H, t, J=5 Hz), 7.09(1H, d, J=8 Hz), 7.75(1H, dd, J=2 Hz, 8 Hz), 8.57(1H, d, J=2 Hz). | |
79% | With diborane; In tetrahydrofuran; at -78 - 20℃; for 16h;Inert atmosphere; | [00543] To a solution of Example 105a (2.16 g, 10.0 mmol) in dry THF (80 mL) was added slowly added BH3/THF (1.0 M, 30 mL) at -78C under nitrogen atmosphere. After addition, the mixture was allowed to stir from -78C to r.t. for 16 h. The reaction was quenched by saturated aqueous K2C03, extracted by EtOAc (50 mL*2), dried over Na2S04, filtered and concentrated. The residue was purified by silica gel chromatography (Petroleum Ether/EtOAc = 30/70) to give the desired product Example 105b (1.6 g, yield 79%) as colorless oil. LCMS [M+l]+ =202.0/204.0 |
51% | With borane-THF; In tetrahydrofuran; at 20℃; for 4h;Inert atmosphere; | To a stirred solution of 2-(5-bromopyridin-2-yl)acetic acid (2 g, 9.25 mmol) in THF (50 mL) was added BH3.THF (12 mL, 12.03 mmol, 1M in THF) drop wise at room temperature under nitrogen and stirred at same temperature for 24 h. The mixture was cooled to 0 C, quenched with water: acetic acid (10 mL, 1:1) and stirred at room temperature for 30 minutes. The reaction mixture was evaporated and resulting residue was diluted with EtOAc (50 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution and water, dried, filtered and evaporated. The crude compound was chromatographed on silica eluting with 40% EtOAc in petroleum ether affording a yellow liquid (950 mg, 51%). M/z = 202.0 (M+H)+. |
Preparation of 6:2-(5-Bromopyridin-2-yl)ethanolUnder N2, a solution of 2-(5-bromopyridin-2-yl)acetic acid (5, 29.75 g) in THF (450 mL) was cooled to 0C. Borane THF complex (1 M in THF, 413.2 mL, 413.2 mmol) was added dropwise, keeping the reaction temperature below 5C. The mixture was allowed to warm to room temperature and stir for 4h. The mixture was cooled to 0C and saturated aqueous K2C03 solution (500 mL) and H20 (500 mL) were added slowly. The mixture was extracted with EtOAc (3x 500 mL). The combined organic layers were washed with brine (500 mL), dried over Na2S04 and filtered. The solvent was removed in vacuo and the residue was purified by column chromatography (silica,Heptane/EtOAc 3:7) yielding compound 6 (10.9 g, 53.9 mmol, 40% over 2 steps). 1 H- NMR (CDCI3, 300 MHz): δ 3.00 (t, 2H, CH2), 3.64 (bs, 1 H, OH), 4.03 (t, 2H, CH2), 7.10 (d, 1 H, ArH), 7.76 (dd, 1 H, ArH), 8.59 (d, 1 H, ArH). | ||
1.09 g | With borane-THF; In tetrahydrofuran; at 5 - 20℃; | Commercially available 2-(5-bromopyridin-2-yl)acetic acid (1.00 g, 4.6 mmol) in tetrahydrofuran (10 mL) is cooled to 5 C. and treated dropwise over 10 minutes with borane-tetrahydrofuran complex (13.9 mL, 13.9 mmol). After stirring at room temperature for 4 hours, the reaction mixture is quenched with saturated aqueous potassium carbonate (20 mL), extracted with ethyl acetate (50 mL), dried over MgSO4, filtered, the solvent removed under reduced pressure, and the crude material purified by column chromatography on silica gel eluting with a gradient of neat heptane to neat ethyl acetate to afford the title compound (1.09 g): m/z (CI) 203 [M+H]. |
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